No human data · Grade D
PE-22-28
PE-22-28 (Spadin Analogue)
Score
48 / 100
Origin
Spadin analog
Target
TREK-1 channel
Status
Preclinical only
TL;DR
01
A synthetic analog of spadin — a natural peptide that blocks the TREK-1 potassium channel, a target linked to rapid-acting antidepressant effects.
02
In mice, the parent peptide spadin produced fast antidepressant-like effects and boosted markers of neuroplasticity (CREB, neurogenesis) within days.
03
PE-22-28 itself has no human trials of any kind, so it is rated No Human Data.
04
The mechanism is a legitimately interesting research direction for depression, but 'interesting target in mice' is where the evidence stops.
05
It is a research chemical with no approval, purity guarantee, or human safety data.
Human trials
None
no clinical data
Preclinical (mice)
Antidepressant-like
rapid onset (days)
Mechanism
TREK-1 inhibition
novel antidepressant target
Approval
None
research chemical
Human safety
Unknown
no data
Part 01 · How it works
Mechanism.
PE-22-28 is a lab analog of spadin, a natural peptide that switches off a specific potassium channel called TREK-1. Blocking TREK-1 has emerged as a promising way to get antidepressant effects quickly — in mice, spadin produced fast mood benefits (in days rather than the weeks SSRIs need) and increased signs of new neuron growth. That's a genuinely interesting target for depression research. But PE-22-28 has never been given to humans in a trial, so whether it helps people, and how safe it is, is completely unknown.
A key that turns off a 'mood-suppressing' channel, giving fast antidepressant effects in mice — with no human trial to say whether it does the same, or what it costs, in people.
TREK-1 inhibition
Spadin/PE-22-28 block the TREK-1 two-pore potassium channel, a mechanism tied to rapid antidepressant action.
Neuroplasticity (animal)
Spadin increased hippocampal CREB phosphorylation and neurogenesis and raised serotonergic firing in mice.
Rapid onset
Antidepressant-like effects within days in rodent behavioral models.
Evidence stage
Preclinical (parent peptide in mice); PE-22-28 has no human trials.
Part 02 · Dosing & administration
How it's taken.
Community-reported · unregulatedValues below reflect commonly reported community protocols for PE-22-28. These are anecdotal and unregulated — not clinically validated and not a recommendation. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.
Standard dose
200-500 mcg
Subcutaneous injection or Intranasal · Once daily
Duration
4–6 weeks typical cycle
·
No human dose exists; circulating community figures (~100–500 mcg/day SC or intranasal) are vendor/forum-derived.
·
All efficacy evidence is mouse behavioral work on this spadin analog — a 4-day sub-chronic course produced antidepressant-like effects and hippocampal neurogenesis (Djillani 2017).
·
Research compound only: no human pharmacokinetics or safety data, and no purity/dose guarantee in research supply.
Need help with reconstitution?
Use the free peptide calculator for dilution, unit conversion, and injection volume.
Part 03 · Safety
Side effects, rare serious events, who shouldn't.
Common
Human tolerability
No human data.
Unknown
Serious · rare
CNS ion-channel effects
Modulating brain potassium channels has unstudied human risks.
Unknown in humans
Long-term human safety
No human safety data.
Unknown
Product-quality risk
Research-chemical supply; purity/dose unknown.
Source-dependent
Absolute · do not use
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to PE-22-28, spadin, or any component
×
Bipolar disorder or mania (may have antidepressant-like effects that could trigger mania)
×
Concurrent use of MAOIs
Relative · discuss first
!
Everyone, for evidence-based use — no human data
!
Depression relying on it in place of evidence-based care — unproven and unsafe to assume
!
Pregnancy or breastfeeding — no data
Interactions
SSRIs (fluoxetine, sertraline)
PE-22-28 blocks TREK-1 potassium channels (same target as some antidepressant mechanisms); additive antidepressant-like effects
Moderate
MAOIs
Combined antidepressant mechanisms may increase risk of serotonin-related adverse effects
Major
Benzodiazepines
Theoretical interaction through shared effects on neuronal excitability; may alter anxiolytic response
Minor
Lithium
Both affect neuronal ion channel function; monitor for additive CNS effects
Moderate
Labs to monitor
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Liver and kidney function
CBC with Differential
Baseline and every 3 months
General safety monitoring
Sodium and Potassium
Baseline and monthly
TREK-1 channel modulation can affect electrolyte handling
Part 04 · Evidence
How strong is the evidence?
48
Grade D
Grade D, No Human Data. PE-22-28 targets a genuinely interesting rapid-antidepressant mechanism (TREK-1) with encouraging mouse data for its parent peptide, but it has no human trials and no human safety data.
Mechanistic plausibility
TREK-1 inhibition is a validated, novel antidepressant target in animal models.
74
Human evidence
No human trials of PE-22-28.
12
Safety & tolerability
No human safety data; CNS ion-channel modulation carries unstudied risks.
42
Durability
No human outcome data.
45
Independence
Mechanism studied by the originating and some other groups; PE-22-28 itself little-studied.
55
Part 05 · Research log
Every study we cite.
We list each study with its methodology, funding source, and our quality grade. Flagged studies aren't dismissed — they're tagged so you can weigh them.
01
2010
PLoS Biology Flagged
Spadin, a sortilin-derived TREK-1 blocker — antidepressant concept
Spadin blocked TREK-1, increased serotonergic firing, produced antidepressant-like effects in five behavioral tests within days, and enhanced hippocampal CREB phosphorylation and neurogenesis — establishing the mechanism PE-22-28 is built on.
Mouse pharmacology + behavior · Foundational mouse work on the parent peptide, not PE-22-28 in humans.
PMID 20405001 ↗
Moderate (preclinical)
Evidence against
What didn't work, and where the evidence is thin.
Every publication is incentivized to tell you a peptide works. We catalogue the null results, failed trials, and mechanism limits we found in the same literature — so you can weigh them against the upside, with your provider.
01
Interesting target in mice — but no human data on PE-22-28
Mechanism limit PLoS Biology · 2010
The rapid-antidepressant evidence is for the parent peptide spadin in mice. PE-22-28 has not been tested in humans in any trial, and its human efficacy and safety are unknown.
What this means: A promising mechanism in rodents is a research lead, not a treatment. Using PE-22-28 for mood means acting entirely without human evidence.
PMID 20405001 ↗
Part 06 · Cost & access
Where it's available, at what price.
United States
Not approved
No approved product; research chemical. No legal consumer medicine.
Grey-market; unregulated
European Union
Not approved
No approved product.
N/A
United Kingdom
Not approved
No approved product.
N/A
Canada
Not approved
No approved product.
N/A
The Peptide Column takes no affiliate commission from any source. PE-22-28 has no human trials and is not approved anywhere; material sold to individuals is a research chemical, unregulated, with unknown human safety and benefit — and depression should be managed with evidence-based care. We link only to clinician-directed care, never to sellers.
Part 07 · Your appointment
Questions to bring.
01
Is there any human safety or efficacy data for PE-22-28?
02
How does TREK-1 inhibition compare to established antidepressant mechanisms?
03
What are the risks of using a compound with no human pharmacokinetic data?
04
Are there better-studied options for cognitive enhancement or mood support?
References
Every citation, numbered.
Citation list. For our editorial read of each study — including bias flags and quality grades — see the Research log above.
- 01. Spadin, a sortilin-derived TREK-1 blocker — antidepressant concept · PLoS Biology, 2010 · PMID 20405001 ↗
- 02. PubMed. Spadin/TREK-1 antidepressant literature